Head and neck squamous cell carcinoma (HNSCC), which is a world-wide health problem, will affect approximately 36,000 Americans with over 7,000 deaths this year. Despite extensive research and introduction of therapeutic advances such as radiation-intensification, prognosis for persons with HNSCC remains among the lowest of all solid tumors.
Intervention with effective chemopreventive agents—to prevent progression or induce regression—at the pre-cancerous stage would greatly improve clinical outcomes. Analogous to other surface origin malignancies, initiated head and neck epithelium undergoes progressive growth disturbances (grades of epithelial dysplasia) prior to conversion to overt carcinoma. Furthermore, many of these dysplastic lesions arise in visible mucosa, making topical application and direct clinical monitoring of lesion progression feasible. Despite obtaining complete surgical excision, many of these dysplastic lesions recur; necessitating sequential surgeries and increasing patient anxieties regarding cancer development.
The buccal mucosa is an attractive site for the localized delivery of therapeutic agents to treat or prevent oral cancer by using a mucoadhesive patch. However, the benefits of this administration route may be limited due to the barrier properties of the buccal mucosa. Since the buccal mucosa is a tissue that is exposed to many foreign agents, the buccal mucosa significant barrier properties may hinder the transport of therapeutically active compounds.
For example, small lipophilic drug molecules with a log P of 1.6-3.3 are generally believed to permeate well because of greater partitioning into the tissue. However, for highly lipophilic drugs with a log P greater than 3.5, a decrease in permeability is observed due to their limited water solubility. In fact, most agents that are better known for enhancing drug permeability through the skin also improve the transport of compounds across the buccal mucosa.
To increase the permeation of drugs, chemical approaches such as the utilization of chemical permeation enhancers (e.g., surfactants, bile salts, and fatty acids) might be only applicable to patch preparations. There is still a need, however, for formulations that can readily cross the buccal mucosa barriers.